Semaglutide 2.4 mg: the latest GLP-1RA approved for obesity
===========================================================

* Ricardo Villela
* Ricardo Correa

*   glucagon-like peptide 1
*   obesity
*   body weight
*   body weights and measures

Overweight and obesity are one of the most relevant health factors; according to the WHO, 39% of people globally are overweight and 13% obese.1 Body weight loss of 3%–5% has been linked to a reduction in risk factors, whereas those with obesity and chronic illness should lose 5%–15% of their body weight to reduce risks.2 Glucose lowering medications, particularly glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs), might result in considerable weight loss.3 Semaglutide 2.4 mg (brand name Wegovy) was recently authorized by the Food and Drug Administration for chronic weight management. It is indicated in patients with a body mass index (BMI)≥30 kg/m2, or a BMI≥27 kg/m2 with comorbidities.4 

The STEPs studies were the landmark trials for assessing the safety and effectiveness of semaglutide. The study proved that weight loss in persons with obesity and type 2 diabetes (DM2), as well as on long-term follow-up, is higher with semaglutide versus placebo.5 The STEP1 Study showed that participants in the semaglutide group lost a mean of 14.9% of their body weight compared with 2.4% in the placebo group after 68 weeks.6 Of note, this study only included overweight or obesity patients. The STEP2 Study included patients with DM2 who were overweight or obese and demonstrated a 9.6% reduction in body weight compared with 3.4% in the placebo group.7 The STEP3 Study incorporated lifestyle treatments in overweight and obese participants with comorbidites; those who received semaglutide plus lifestyle interventions lost 16% of their body weight, whereas the placebo group lost 5.7%.8 The STEP4 Study allocated all patients with semaglutide up to week 20, later they randomized the group into semaglutide or placebo, noticing that patients in the semaglutide group lost 7.9% of their body weight, whereas patients in the placebo group gained 6.9% of their body weight following randomization.9 

Wegovy is administered weekly through subcutaneous injection at a dose of 2.4 mg, as several clinical studies have shown that weekly treatment is as consistent as daily administration.5 Weight reduction efficiency is dose-dependent, with Wegovy being more effective than Ozempic (semaglutide used for diabetes with a maximum dose of 1.0 mg).10 The side effects of semaglutide have proven to be no different or intense than any other GLP-1RAs.11 12 In addition, a recent study found that patients treated with semaglutide for obesity or diabetes had a reduced risk at cardiovascular events including cardiovascular death, non-fatal myocardial infarction, or non-fatal strokes.10 

In conclusion, semaglutide 2.4 mg has been shown to be more successful than other GLP-1RAs in terms of weight reduction.10 11 When prescribing semaglutide, physicians must evaluate a number of criteria, the most significant of which is the price, since most insurance does not cover these therapies.4 Nonetheless, the numerous advantages of semaglutide 2.4 mg makes it a great medication to consider for these populations, as it can enhance their weight reduction maintenance and quality of life, and add some cardiovascular protection.

## Ethics statements

### Patient consent for publication

Not applicable.

### Ethics approval

This study does not involve human participants.

## Footnotes

*   Twitter @drricardocorrea

*   Contributors All authors have substantially participated in the preparation and agree to be accountable for all aspects of work related to this Editorial. RV contributed to the conception, literature search, writing, editing, revision, and final approval of the manuscript. RRC contributed to the conception, literature search, writing, editing, revision, and final approval of the manuscript.

*   Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

*   Competing interests None declared.

*   Provenance and peer review Commissioned; internally peer reviewed.

## References

1.  Obesity and overweight. Available: [https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight](https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight) [Accessed 15 Oct 2021].
    
    

2.   Lundgren JR , Janus C , Jensen SBK , et al . Healthy weight loss maintenance with exercise, liraglutide, or both combined. N Engl J Med 2021;384:1719–30.[doi:10.1056/NEJMoa2028198](http://dx.doi.org/10.1056/NEJMoa2028198) pmid:http://www.ncbi.nlm.nih.gov/pubmed/33951361 
    
    [PubMed](/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fjim%2F70%2F1%2F3.atom) 

3.   Bessesen DH , Van Gaal LF . Progress and challenges in anti-obesity pharmacotherapy. Lancet Diabetes Endocrinol 2018;6:237–48.[doi:10.1016/S2213-8587(17)30236-X](http://dx.doi.org/10.1016/S2213-8587(17)30236-X) pmid:http://www.ncbi.nlm.nih.gov/pubmed/28919062 
    
    [PubMed](/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fjim%2F70%2F1%2F3.atom) 

4.  High dose Semaglutide for weight loss and cardiometabolic risk reduction in Overweight/Obesity. American College of cardiology. Available: [https://www.acc.org/latest-in-cardiology/articles/2021/07/21/14/06/http%3a%2f%2fwww.acc.org%2flatest-in-cardiology%2farticles%2f2021%2f07%2f21%2f14%2f06%2fhigh-dose-semaglutide-for-weight-loss-and-cardiometabolic-risk-reduction](https://www.acc.org/latest-in-cardiology/articles/2021/07/21/14/06/http%3a%2f%2fwww.acc.org%2flatest-in-cardiology%2farticles%2f2021%2f07%2f21%2f14%2f06%2fhigh-dose-semaglutide-for-weight-loss-and-cardiometabolic-risk-reduction) [Accessed 31 Oct 2021].
    
    

5.   Kushner RF , Calanna S , Davies M , et al . Semaglutide 2.4 mg for the treatment of obesity: key elements of the STEP trials 1 to 5. Obesity 2020;28:1050–61.[doi:10.1002/oby.22794](http://dx.doi.org/10.1002/oby.22794) 
    
    

6.   Wilding JPH , Batterham RL , Calanna S , et al . Once-Weekly Semaglutide in adults with overweight or obesity. N Engl J Med 2021;384:989–1002.[doi:10.1056/NEJMoa2032183](http://dx.doi.org/10.1056/NEJMoa2032183) pmid:http://www.ncbi.nlm.nih.gov/pubmed/33567185 
    
    [CrossRef](/lookup/external-ref?access_num=10.1056/NEJMoa2032183&link_type=DOI) 
    
    [PubMed](/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fjim%2F70%2F1%2F3.atom) 

7.   Davies M , Færch L , Jeppesen OK , et al . Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (step 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet 2021;397:971–84.[doi:10.1016/S0140-6736(21)00213-0](http://dx.doi.org/10.1016/S0140-6736(21)00213-0) pmid:http://www.ncbi.nlm.nih.gov/pubmed/33667417 
    
    [CrossRef](/lookup/external-ref?access_num=10.1016/S0140-6736(21)00213-0&link_type=DOI) 
    
    [PubMed](/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fjim%2F70%2F1%2F3.atom) 

8.   Wadden TA , Bailey TS , Billings LK , et al . Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity. JAMA 2021;325:1403–11.[doi:10.1001/jama.2021.1831](http://dx.doi.org/10.1001/jama.2021.1831) 
    
    [PubMed](/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fjim%2F70%2F1%2F3.atom) 

9.   Rubino D , Abrahamsson N , Davies M , et al . Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity. JAMA 2021;325:1414–12.[doi:10.1001/jama.2021.3224](http://dx.doi.org/10.1001/jama.2021.3224) 
    
    

10.  Singh G , Krauthamer M , Bjalme-Evans M . Wegovy (semaglutide): a new weight loss drug for chronic weight management. J Investig Med 2022;70:5–13.[doi:10.1136/jim-2021-001952](http://dx.doi.org/10.1136/jim-2021-001952) pmid:http://www.ncbi.nlm.nih.gov/pubmed/34706925 
    
    [Abstract/FREE Full Text](/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamltIjtzOjU6InJlc2lkIjtzOjY6IjcwLzEvNSI7czo0OiJhdG9tIjtzOjE2OiIvamltLzcwLzEvMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

11.  Lingvay I , Hansen T , Macura S , et al . Superior weight loss with once-weekly semaglutide versus other glucagon-like peptide-1 receptor agonists is independent of gastrointestinal adverse events. BMJ Open Diabetes Res Care 2020;8:e001706. [doi:10.1136/bmjdrc-2020-001706](http://dx.doi.org/10.1136/bmjdrc-2020-001706) pmid:http://www.ncbi.nlm.nih.gov/pubmed/33115821 
    
    [Abstract/FREE Full Text](/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NjoiYm1qZHJjIjtzOjU6InJlc2lkIjtzOjExOiI4LzIvZTAwMTcwNiI7czo0OiJhdG9tIjtzOjE2OiIvamltLzcwLzEvMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

12.  Blundell J , Finlayson G , Axelsen M , et al . Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab 2017;19:1242–51.[doi:10.1111/dom.12932](http://dx.doi.org/10.1111/dom.12932) pmid:http://www.ncbi.nlm.nih.gov/pubmed/28266779 
    
    [PubMed](/lookup/external-ref?access_num=28266779&link_type=MED&atom=%2Fjim%2F70%2F1%2F3.atom)